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Quantitative lung T cell responses aid the rapid diagnosis of pulmonary tuberculosis

Dheda, Keertan and Zyl-Smit, Richard N. van and Meldau, Richard and Meldau, Surita and Symons, Gregory and Khalfey, Hoosein and Govender, Neville and Rosu, Valentina and Sechi, Leonardo Antonio and Maredza, Alice and Semple, Patricia L. and Whitelaw, Andrew and Wainwrite, Helen C. and Badri, Motasim and Dawson, Rodney and Bateman, Eric D. and Zumla, Alimuddin (2009) Quantitative lung T cell responses aid the rapid diagnosis of pulmonary tuberculosis. Thorax, Vol. 64 (10), p. 847-853. eISSN 1468-3296. Article.

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DOI: 10.1136/thx.2009.116376

Abstract

Background: The diagnosis of smear-negative pulmonary tuberculosis (TB) is problematic. There are limited data on the profile of alveolar TB antigen-specific T cells, and their utility for the rapid immunodiagnosis of pulmonary TB is unclear.
Methods: Antigen-specific interferon γ (IFNγ) responses to the RD-1 antigens ESAT-6 and CFP-10 (T-SPOT.TB and QuantiFERON-TB-Gold-In-Tube), heparin-binding haemagglutinin and purified protein derivative were evaluated, using alveolar lavage cells, in 91 consecutively recruited South African patients suspected of having TB.
Results: Of 85 evaluable patients (29% HIV+), 24, 11, 48 and 2 had definite TB, probable TB, non-TB and an uncertain diagnosis, respectively. Between 34% (T-SPOT.TB) and 41% (QuantiFERON-TB-Gold-In-Tube) of all test results were inconclusive. Failure of the positive control was significantly higher with the QuantiFERON-TB-Gold-In-Tube than with T-SPOT.TB (85% vs 46% of inconclusive results; p = 0.001). Using staphylococcal enterotoxin B, compared with phytohaemagglutinin, substantially reduced failure of the positive control (25% to 3%; p = 0.02). In evaluable samples, when the definite and non-TB groups were used for outcome analysis, the percentage sensitivity, specificity, positive predictive value and negative predictive value for T-SPOT.TB (≥20 spots/million alveolar mononuclear cells) and QuantiFERON-TB-Gold-In-Tube (0.35 IU/ml) were 89, 94, 89 and 94% (n = 55) and 55, 86, 77 and 69% (n = 46), respectively. Rapid diagnosis of TB was achieved more frequently with T-SPOT.TB than with smear microscopy (14/24 (58%) vs. 7/24 (29%) of definite TB cases; p = 0.02). Heparin-binding haemagluttinin and purified protein derivative alveolar lymphocyte IFNγ responses had poor performance outcomes.
Conclusion: Provided evaluable results are obtained, the RD-1, but not the heparin-binding haemagglutinin or purified protein derivative, alveolar lymphocyte IFNγ ELISPOT response is a useful rapid immunodiagnostic test for TB. However, test utility in high-burden settings may be limited by the high proportion of inconclusive results.

Item Type:Article
ID Code:3506
Status:Published
Refereed:Yes
Uncontrolled Keywords:Polmonar tubercolosis, diagnosis, T cell
Subjects:Area 06 - Scienze mediche > MED/07 Microbiologia e microbiologia clinica
Divisions:001 Università di Sassari > 01 Dipartimenti > Scienze biomediche
Publisher:BMJ Publishing Group
eISSN:1468-3296
Deposited On:22 Jan 2010 10:26

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